Function of a mycobacterial major facilitator superfamily pump requires a membrane-associated lipoprotein
Function of a mycobacterial major facilitator superfamily pump requires a membrane-associated lipoprotein
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DOI：
10.1128/jb.01046-07
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发表时间：
2008-03-01
影响因子：
3.2
通讯作者：
Rubin, Eric J.
中科院分区：
文献类型：
--
作者：
Farrow, Mary F.;Rubin, Eric J.
lprG-Rv 1410 c操纵子对于结核分枝杆菌在感染期间的存活至关重要，但对其蛋白质的功能知之甚少。LprG是一种脂蛋白，Rv 1410 c编码主要易化超家族小分子转运蛋白P55。P55可能将小分子输出到细菌细胞外，但LprG的功能尚不清楚。在耻垢分枝杆菌中同源操纵子的缺失对溴化乙锭更敏感，并且通过来自M的完整操纵子恢复耐药性。结核多药耐药泵抑制剂利血平抑制了两种野生型M。smeglavin和互补突变体，这表明P55介导的运输是负责耐药性和溴化乙锭是一种新的底物P55。除了对溴化乙锭的超敏反应之外，缺乏lprG-Rv 1410 c操纵子的细胞显示异常的集落形态，并且滑动运动性有缺陷，这些特性表明细胞壁组成的改变。引人注目的是，溴化乙锭转运和正常的细胞表面特性都需要功能性P55和LprG，因为单独的P55和LprG都不足以恢复缺失突变体的功能。因此，P55需要细胞表面脂蛋白来维持正常功能。
The lprG-Rv1410c operon is critical for the survival of Mycobacterium tuberculosis during infection, but very little is known about the functions of its proteins. LprG is a lipoprotein, and Rv1410c encodes the major facilitator superfamily small molecule transporter P55. P55 likely exports small molecules outside of the bacterial cell, but the function of LprG is unclear. A deletion of the homologous operon in Mycobacterium smegmatis is more susceptible to ethidium bromide, and drug resistance is restored by the intact operon from M. tuberculosis. The multidrug resistance pump inhibitor reserpine inhibits resistance to ethidium bromide in both wild-type M. smegmatis and the complemented mutant, suggesting that P55-mediated transport is responsible for drug resistance and that ethidium bromide is a novel substrate for P55. In addition to hypersensitivity to ethidium bromide, cells that lack the lprG-Rv1410c operon display abnormal colony morphology and are defective for sliding motility, properties that suggest an alteration of cell wall composition. Strikingly, both ethidium bromide transport and normal cell surface properties require functional P55 and LprG, as neither alone is sufficient to restore function to the deletion mutant. Thus, P55 requires the cell surface lipoprotein for normal function.